P491: PREDICTIVE FACTORS OF DIFFERENTIATION SYNDROME IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA
Authors: M. Ben Salah, M. Bchir, R. Berred, R. Kharrat, L. Aissaoui, Y. Ben Abdennebi, R. Ben Lakhal, H. Ben neji, B. Meddeb
Journal: HemaSphere (2022)

Background: Differentiation syndrome (DS) may be a life-threatening complication in patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and anthracycline chemotherapy. Identifying high risk patients enables a more efficient follow up and an optimal prophylaxis strategy. Aims: The aim of this study was to analyze the incidence, characteristics, and the risk factors of DS occurring during induction treatment in APL patients treated with ATRA and anthracycline. Methods: We conducted a retrospective single-center study, including patients diagnosed with APL between 2010 and 2019 in our department and treated with ATRA and chemotherapy according to PETHEMA protocols LPA99 and LPA2005. Obesity, renal failure and a high risk (according to the Sanz score) represented an indication for a DS prophylaxis prescription, using whether prednisone (LPA99) or dexamethasone (LPA2005). A univariate and a multivariate analysis were conducted, in order to identify predictive factors of DS. Results: Ninety patients were included in our study, with an average age of 34 years old. According to Frankel’s diagnostic criteria, 16 patients (18%) experienced a DS, with a mean age of 39 years [13-71 years], and a sex ratio of 0.6. Half of this group was classified as high risk according to the Sanz score, 44% as intermediate risk, and 6% as low risk. A severe differentiation syndrome was described in 7 patients (44%). The syndrome occurred at a median of 4 days after the start of induction therapy [2-26 days]. A Prophylaxis had been prescribed for 10 patients (62.5%): 8 were classified as high risk, and 2 had obesity. In order to identify the risk factors of DS, the following parameters were analyzed: age, sex, performance status, Body Mass Index, clinical presentation at diagnosis, treatment protocol, Sanz score, creatinine level, LDH level, hemoglobin level, white blood cell (WBC) count, platelets, cytological type, PML-RARa variant, CD2, CD15, CD34, CD56 expression, fibrinogen level, prothrombin time, presence of disseminated intravascular coagulopathy (DIC), occurrence of bleeding and thromboembolic complications, and corticosteroid prophylaxis. The univariate analysis identified a statistically significant difference between the group of patients with DS and the one without, for the following factors: WBC greater than 50G/L (31,3% versus 8,1%; p=0,02), the presence of DIC at diagnosis (81.3% versus 18.7%; p=0.01), the expression of CD34 (p=0.017), the LDH level (a median of 307 versus 590; p=0.026), and the treatment protocol LPA 99(11 patients (68.8%) treated according to LPA99 versus 5 (31,3%) treated according to LPA2005; p=0.003). Upon multivariate analysis, WBC count greater than 50 G/L (p=0,007), the presence of DIC at diagnosis (p=0,03), and the treatment protocol LPA99 (p=0,02), remained independent risk factors of DS (Table1). Image:Summary/Conclusion: Differentiation syndrome is a significant complication secondary to the ground-breaking treatment of APL. It is necessary to accurately identify high risk patients in order to elaborate effective risk-adapted prophylaxis and treatment.